Local anesthetics Flashcards
The axons of peripheral nerves differ in their
size, structure, speed of conduction, myelination, and sensitivity to the local anesthetic blockade
Conduction velocity is increased by
myelination and a wider axonal diameter
What are the three major classes of peripheral nerves?
A, B & C
In the clinical setting, local anesthetics inhibit peripheral nerves in the following order:
B fibers
C fibers
Small diameter A fibers (delta, gamma)
Large diameter A fibers (alpha, beta)
Regression of blockade occurs in the
opposite order of block onset
What is saltatory conduction?
when myelin insulates the axon and allows the electrical signal to skip along only the uninsulated regions
Conduction velocity is a measure of
how fast an axon transmits the axon potential
What is the function of B fibers?
preganglionic ANS fibers
What is the function of C fibers with a sympathetic subtype?
postganglionic ANS fibers
What is the function of C fibers with a dorsal root subtype?
slow pain
temperature
touch
What is the function of A alpha fibers?
skeletal muscle- motor proprioception
What is the function of A beta fibers?
touch
pressure
What is the function of A gamma fibers
skeletal muscle-tone
What is the function of A delta fibers?
fast pain
temperature
touch
What is Cm?
a unit of measure that quantifies the concentration of local anesthetic that is required to block conduction
minimum effective concentration
Fibers that are more easily blocked have a _________ Cm.
lower
Cm is typically _____________ in nerves with a wider diameter
higher
Cm is reduced by
higher tissue pH or a high frequency of nerve stimulation
Which peripheral nerve fiber type is not myelinated?
C fibers
Local anesthetics can bind to the voltage-gated sodium channel when it is in the:
a. resting and active states
b. resting and inactive states
c. active and inactive states
d. active state only
c. active and inactive state
What are the three possible states that the sodium channel can exist in?
- resting (nonconducting)
- active (conduction)
- inactive (nonconducting)
Local anesthetics reversibly bind to
the alpha subunit of the voltage-gated sodium channel
Through their binding of the voltage-gated sodium channel, local anesthetics
reduce sodium conductance and block nerve conduction
______________ says that local anesthetics can only bind to sodium channels in their active (open) and inactive (closed refractory) states.
The guarded receptor hypothesis
What determines that state of the sodium channel?
voltage
What is resting state voltage?
-70 mV
At resting membrane potential, the channel is
closed
What is the active state voltage?
-70 mV to +35 mV
What happens to the Na channel in the active state?
when threshold potential is reached, the channel opens
allows Na+ to follow its concentration gradient (outside to inside)
What is the voltage in the inactive state?
+35 to -70 mV
What happens in the inactive stage?
the channel is closed
the inactivation gate plugs the channel until the resting membrane is re-established
restoration of the resting membrane potential converts the channel from the inactive state to the resting state
Can the channel be opened in the inactive state?
no
Can the channel be opened in the resting state?
it’s closed but able to be opened
What is a use-dependent or phasic blockade?
the more frequently the nerve is depolarized and voltage-gated sodium channels open, the more time available for binding ad the faster the nerve will be blocked
Local anesthetics: (select 2)
a. increase threshold potential
b. decrease resting membrane potential
c. have no effect on threshold potential
d. have no effect on resting membrane potential
c. have no effect on threshold potential
d. have no effect on resting membrane potential
In the peripheral nerve the resting membrane potential is
-70 mV
In the peripheral nerve, the threshold potential is
-55 mV
Describe depolariziation.
An AP is created when an electrical stimulus opens voltage-gated sodium channels
sodium enters the cell
Once the threshold potential is achieved, the cell depolarizes and propagates an action potential
Wave of depolarization travels downstream (since upstream portion is in its refractory phase)
Describe repolarization
The voltage gated Na channels inactivate after a set time
increased potassium conductance restores transmembrane potential to RMP
the Na/K-ATPase maintains RMP until the nerve is depolarized again
When a critical number of sodium channels are blocked by local anesthetic,
the cell can’t depolarize and the action potential can’t be propagated
What three things influence resting membrane potential?
- chemical force (concentration gradient)
- electrostatic counterforce
- Na+/K+ ATPase (3 for 2 in)
What is the primary determinant of resting membrane potential?
serum K+
Decreased serum K+ causes the RMP to
become more negative
Increased serum K+ causes the RMP to
become more positive
What is the primary determinant of threshold potential?
serum Ca2+
Decreased serum Ca2+ causes the threshold potential to
become more negative
Increased serum Ca2+ causes the threshold potential to
become more positive
Depolarization is __________ phenomenon
all or none- once it begins it cannot be stopped
When RMP is closer to TP, the cell is
easier to depolarize
When RMP is further from TP, the cell is
harder to depolarize
A cell depolarizes when
Na+ or Ca+ enters a cell
A cell repolarizes when
K+ leaves or Cl- enters the cell
